[Management of an amnesic patient]. / Prise en charge d'un patient amnésique.

MANAGEMENT OF AN AMNESIC PATIENT. Until the early 1980s, neuropsychological rehabilitation of amnesic syndromes was limited to extensive repeated practice ('cognitive drill'). The ineffectiveness of these methods is now acknowledged, if the therapeutic target concerns daily life. On the other hand, a serie of therapeutic methods have shown robust, albeit modest, efficacy. These therapies are mainly based on the facilitation of impaired processes, on the learning of specific skills or on the use of external memory aids. Mostly applied within clinical neuropsychology settings, they have in common the need to identify a relevant goal in daily life. These methods are likely to lead to robust benefits in terms of independence and quality of life and demonstrate that the amnesic syndrome does not hinder any new learning abilities. Promising avenues in the field concern the combination of techniques and the use of technological aids based on neurocognitive models of human memory. Their effectiveness still relies on a highly tailored, individual approach, focusing on what makes each patient unique in terms of needs and disabilities.

PRISE EN CHARGE D'UN PATIENT AMNÉSIQUE. Jusqu'au début des années 1980, les thérapies non médicamenteuses du syndrome amnésique se limitaient à des exercices de mémoire répétitifs. Leur inefficacité est aujourd'hui établie, dès lors que l'objectif thérapeutique concerne la vie quotidienne. En revanche, une série d'autres méthodes thérapeutiques ont montré une efficacité robuste, quoique modeste. Ces thérapies reposent principalement sur la facilitation des processus déficitaires, sur l'apprentissage d'aptitudes spécifiques, ou sur le recours à des aides externes. Mises en oeuvre par la neuropsychologie clinique, elles ont en commun la nécessité d'identifier un objectif précis et pertinent sur les actes de la vie quotidienne. Susceptibles d'aboutir à des bénéfices en matière d'autonomie et de qualité de vie, ces méthodes démontrent que le syndrome amnésique n'obère pas toute possibilité d'apprentissage. Les perspectives concernent la combinaison de techniques entre elles et le recours à des aides technologiques fondées sur les modèles neurocognitifs de la mémoire humaine. Leur efficacité reste dépendante d'une approche individualisée, centrée sur les singularités du patient.

Building memories on prior knowledge: behavioral and fMRI evidence of impairment in early Alzheimer's disease.

Impaired memory is a hallmark of prodromal Alzheimer's disease (AD). Prior knowledge associated with the memoranda improves memory in healthy individuals, but we ignore whether the same occurs in early AD. We used functional MRI to investigate whether prior knowledge enhances memory encoding in early AD, and whether the nature of this prior knowledge matters. Patients with early AD and Controls underwent a task-based fMRI experiment where they learned face-scene associations. Famous faces carried pre-experimental knowledge (PEK), while unknown faces with which participants were familiarized prior to learning carried experimental knowledge (EK). Surprisingly, PEK strongly enhanced subsequent memory in healthy controls, but importantly not in patients. Partly nonoverlapping brain networks supported PEK vs. EK associative encoding in healthy controls. No such networks were identified in patients. In addition, patients displayed impaired activation in a right sub hippocampal region where activity predicted successful associative memory formation for PEK stimuli. Despite the limited sample sizes of this study, these findings suggest that the role prior knowledge in new learning might have been so far overlooked and underestimated in AD patients. Prior knowledge may drive critical differences in the way healthy elderly and early AD patients learn novel associations.

Refining understanding of working memory buffers through the construct of binding: Evidence from a single case informs theory and clinical practise.

Binding operations carried out in working memory enable the integration of information from different sources during online performance. While available evidence suggests that working memory may involve distinct binding functions, whether or not they all involve the episodic buffer as a cognitive substrate remains unclear. Similarly, knowledge about the neural underpinnings of working memory buffers is limited, more specifically regarding the involvement of medial temporal lobe structures. In the present study, we report on the case of patient KA, with developmental amnesia and selective damage to the whole hippocampal system. We found that KA was unable to hold shape-colours associations (relational binding) in working memory. In contrast, he could hold integrated coloured shapes (conjunctive binding) in two different tasks. Otherwise, and as expected, KA was impaired on three relational memory tasks thought to depend on the hippocampus that are widely used in the early detection of Alzheimer's disease. Our results emphasize a dissociation between two binding processes within working memory, suggesting that the visuo-spatial sketchpad could support conjunctive binding, and may rely upon a large cortical network including sub-hippocampal structures. By contrast, we found evidence for a selective impairment of relational binding in working memory when the hippocampal system is compromised, suggesting that the long-term memory deficit observed in amnesic patients may be related to impaired short-term relational binding at encoding. Finally, these findings may inform research on the early detection of Alzheimer's disease as the preservation of conjunctive binding in KA is in sharp contrast with the impaired performance demonstrated very early in this disease.

Superior explicit memory despite severe developmental amnesia: In-depth case study and neural correlates.

The acquisition of new semantic memories is sometimes preserved in patients with hippocampal amnesia. Robust evidence for this comes from case reports of developmental amnesia suggesting that low-to-normal levels of semantic knowledge can be achieved despite compromised episodic learning. However, it is unclear whether this relative preservation of semantic memory results from normal acquisition and retrieval or from residual episodic memory, combined with effortful repetition. Furthermore, lesion studies have mainly focused on the hippocampus itself, and have seldom reported the state of structures in the extended hippocampal system. Preserved components of this system may therefore mediate residual episodic abilities, contributing to the apparent semantic preservation. We report an in-depth study of Patient KA, a 27-year-old man who had severe hypoxia at birth, in which we carefully explored his residual episodic learning abilities. We used novel speeded recognition paradigms to assess whether KA could explicitly acquire and retrieve new context-free memories. Despite a pattern of very severe amnesia, with a 44-point discrepancy between his intelligence and memory quotients, KA exhibited normal-to-superior levels of knowledge, even under strict time constraints. He also exhibited normal-to-superior recognition memory for new material, again under strict time constraints. Multimodal neuroimaging revealed an unusual pattern of selective atrophy within each component of the extended hippocampal system, contrasting with the preservation of anterior subhippocampal cortices. A cortical thickness analysis yielded a pattern of thinner but also thicker regional cortices, pointing toward specific temporal lobe reorganization following early injury. We thus report the first case of superior explicit learning and memory in a severe case of amnesia, raising important questions about how such knowledge can be acquired.

What semantic dementia teaches us about the functional organization of the left posterior fusiform gyrus.

After demonstrating the relative preservation of fruit and vegetable knowledge in patients with semantic dementia (SD), we sought to identify the neural substrate of this unusual category effect. Nineteen patients with SD performed a semantic sorting task and underwent a morphometric 3T MRI scan. The grey-matter volumes of five regions within the temporal lobe were bilaterally computed, as well as those of two recently described areas (FG1 and FG2) within the posterior fusiform gyrus. In contrast to the other semantic categories we tested, fruit and vegetable scores were only predicted by left FG1 volume. We therefore found a specific relationship between the volume of a subregion within the left posterior fusiform gyrus and performance on fruits and vegetables in SD. We argue that the left FG1 is a convergence zone for the features that might be critical to successfully sort fruits and vegetables. We also discuss evidence for a functional specialization of the fusiform gyrus along two axes (lateral medial and longitudinal), depending on the nature of the concepts and on the level of processing complexity required by the ongoing task.

Brain structural, functional, and cognitive correlates of recent versus remote autobiographical memories in amnestic Mild Cognitive Impairment.

Deficits in autobiographical memory appear earlier for recent than for remote life periods over the course of Alzheimer's disease (AD). The present study aims to further our understanding of this graded effect by investigating the cognitive and neural substrates of recent versus remote autobiographical memories in patients with amnestic Mild Cognitive Impairment (aMCI) thanks to an autobiographical fluency task. 20 aMCI patients and 25 Healthy elderly Controls (HC) underwent neuropsychological tests assessing remote (20-to-30 years old) and recent (the ten last years) autobiographical memory as well as episodic and semantic memory, executive function and global cognition. All patients also had a structural MRI and an FDG-PET scan. Correlations were assessed between each autobiographical memory score and the other tests as well as grey matter volume and metabolism. Within the aMCI, performances for the remote period correlated with personal semantic memory and episodic memory retrieval whereas performances for the recent period only correlated with episodic memory retrieval. Neuroimaging analyses revealed significant correlations between performances for the remote period and temporal pole and temporo-parietal cortex volumes and anterior cingulate gyrus metabolism, while performances for the recent period correlated with hippocampal volume and posterior cingulate, medial prefrontal and hippocampus metabolism. The brain regions related with the retrieval of events from the recent period showed greater atrophy/hypometabolism in aMCI patients compared to HC than those involved in remote memories. Recall of recent memories essentially relies on episodic memory processes and brain network while remote memories also involve other processes such as semantic memory. This is consistent with the semanticization of memories with time and may explain the better resistance of remote memory in AD.

When the zebra loses its stripes but is still in the savannah: results from a semantic priming paradigm in semantic dementia.

Studies using semantic priming paradigms to measure the integrity of the features underlying concepts in semantic dementia (SD) reported differential impairment, in that functional features appeared to be more robust to brain damage than other features, such as perceptual ones. However, these prior studies were single case reports and the inclusion of too many heterogeneous features under the "functional features" heading casts doubts on their apparent preservation. To verify the robustness of functional features compared with perceptual ones, we carried out a group study where we deliberately restricted the exploration of semantic features to two clearly defined types of attribute: visuoperceptual ("visual") versus contextual-functional ("contextual"). We administered an implicit lexical-decision priming task to 8 SD patients and 31 healthy matched controls, at baseline. Four of the patients underwent a follow-up assessment at one year. For controls, we found a significant priming effect in the visual condition, but not in the contextual one, whereas the SD group exhibited the reverse pattern of performances. The follow-up data provided evidence of the robustness of the dissociation between priming performances in the two attribute conditions. The fact that a particular priming effect was observed in the SD patients but not in controls could be regarded as a sign of semantic disequilibrium. Since perceptual features have been shown to be a core determinant of similarity-based/taxonomic relationships, whereas complementary-based/thematic processing relies mainly on contextual relationships, we interpreted our findings in terms of the differential recruitment of one of the two systems of semantic relationships (taxonomic vs. thematic). Moreover, these two distinct and parallel systems have previously been reported to coexist - and compete - in healthy adults. We thus argue that controls automatically drew on similarity-based/taxonomic relationships, leading to a significant priming effect for visual features but not for contextual ones. By contrast, their impaired perceptual features forced the SD patients to resort to the system of thematic relationships.

Relative category-specific preservation in semantic dementia? Evidence from 35 cases.

Category-specific deficits have rarely been reported in semantic dementia (SD). To our knowledge, only four previous studies have documented category-specific deficits, and these have focused on the living versus non-living things contrast rather than on more fine-grained semantic categories. This study aimed to determine whether a category-specific effect could be highlighted by a semantic sorting task administered to 35 SD patients once at baseline and again after 2 years and to 10 Alzheimer's disease patients (AD). We found a relative preservation of fruit and vegetables only in SD. This relative preservation of fruit and vegetables could be considered with regard to the importance of color knowledge in their discrimination. Indeed, color knowledge retrieval is known to depend on the left posterior fusiform gyrus which is relatively spared in SD. Finally, according to predictions of semantic memory models, our findings best fitted the Devlin and Gonnerman's computational account.

[Semantic dementia]. / La démence sémantique.

Semantic dementia (SD) is characterized by an assymetric atrophy of the temporal lobes and, clinically, by an impairment of the semantic memory associated to psychobehavioral symptoms. The concept of SD was defined in 1989 and still remains controversial. Some authors consider DS as a specific entity, others as part of the frontotemporal dementia (FTD) or a variant of the progressive aphasia syndrome. Many arguments tend to include SD in the FTD. However, SD presents a high interest for the comprehension of the organization of semantic memory in man, and is often associated with specific histopathologic lesions (ubiquitine positive and tau negative). Therefore SD should be considered as a clinical specific entity.